Interferon-driven immune dysregulation in down syndrome: A review of the evidence

Howard Chung, Peter H.R. Green, Timothy C. Wang, Xiao Fei Kong

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Down syndrome (DS) is a unique genetic disease caused by the presence of an extra copy of chromosome 21, which carries four of the six interferon receptor (IFN-R) genes on its long arm. Recent studies reporting higher levels of interferon-stimulated gene (ISG) expression in primary immune cells studied ex vivo have suggested that the additional copies of the IFN-R genes in DS result in mild interferonopathy. In this review, we analyze the potential clinical and immunological impacts of this interferonopathy in DS. We per-formed a literature review to explore the epidemiology and risks of celiac disease, type 1 diabetes, thyroid dysfunction, mucocutaneous manifestations, infectious diseases (including COVID-19), and Alzheimer’s disease in individuals with DS relative to the general population with or without iatrogenic exposure to interferons. We analyzed immunophenotyping data and the current experimental evidence concerning IFN-R expression, constitutive JAK-STAT activation, and ISG overexpression in DS. Despite the lack of direct evidence that implicating this mild interferonopathy directly in illnesses in individuals with DS, we high-light the challenges ahead and directions that could be taken to determine more clearly the biological impact of interferonopathy on various immune-related conditions in DS.

Original languageEnglish (US)
Pages (from-to)5187-5200
Number of pages14
JournalJournal of Inflammation Research
StatePublished - 2021
Externally publishedYes


  • Celiac disease
  • Down syndrome
  • Gene dosage effect
  • Interferon receptors
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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